Prusias was born to Prusias I and Apama III in 220 BC. His father died in 189 BC,[1] at which point became the king of Bithynia. Prusias joined with the king of Pergamon, Eumenes II in a war against King Pharnaces I of Pontus (181–179 BC).[2] He later invaded the territories of Pergamon (156–154 BC), only to be defeated, and the Pergamenes insisted on heavy reparations, which included 500 talents and "twenty decked ships".[3] Prusias married his maternal cousin Apame IV, a sister of Perseus of Macedon and a princess from the Antigonid dynasty,[4] by whom he had a son called Nicomedes II and a daughter, also called Apama, who married Dyegilos,[5] son of Cotys IV, King of Thrace, and wife Semestra.

Prusias was praised by the Aetolians on account of his behavior and benefactions towards them.[6]

Towards the end of his life, Prusias II had children by a later wife, and wanted to make them his heirs in place of Nicomedes.[7] He sent Nicomedes to Rome to ask its help in reducing the amount of these reparations, and directed the co-ambassador, Menas, to kill Nicomedes if the mission was unsuccessful.[8] Despite the failure of the mission, Nicomedes persuaded Menas to betray Prusias, and Nicomedes declared himself king.[9] Prusias had to renounce the kingship in favor of his son and ended up being murdered himself instead in 149 BC.[10]